Two classes of mycobacterial glycolipids, cord factor (trehalose 6,6' dimycolate) and the sulfatides of M. tuberculosis have achieved prominence as probable virulence factors in M. tuberculosis because of individual and synergistic toxic qualities, and for the sulfatides especially, because of their powerful antagonism of phagosome-lysosome fusion--as in cultured macrophages. Cord factor has also assumed prominence as an apparently required cofactor with other substances in antitumor activity. Our studies will test additional biological activities of the sulfatides which may implicate them in pathogenesis, seek to define how these and other polyanionic agents induce the lysosomal dysfunction and how this block may be antagonized or relieved. Protein conjugates which elicit antibodies with trehalose specificity have been prepared, and analogs will be made for obtaining antisera with trehalose sulfate specificity in an effort to antagonize this behavior of the sulfatides. We are also synthesizing pseudo cord factors (with specifically altered functional groups, based on trehalose 6,6' dicarboxylic acid) whose toxicity and activity in tumor regression in strain 2 guinea pigs are being assessed so as to gain more understanding of structure-activity relations, and hopefully to provide inexpensive substitutes for cord factor to be used in tumor immunotherapy. BIBLIOGRAPHIC REFERENCES: Saito, R., A. Tanaka, K. Sugiyama, I. Azuma, Y. Yamamura, M. Kato and M.B. Goren. Adjuvant effect of cord factor, a mycobacterial lipid. Infect. Immunity 13:776-781 (1976). Goren, M.B. Phagocyte lysosomes: interactions with infectious agents, phagosomes, and experimental perturbations in function. Ann. Rev. Microbiol. 31:507-533 (1977), in press.